Pharmaceutical compositions comprising moricizine hydrochloride (10-(3-morpholinopropionyl)-phenothiazine-2-carbamic acid ethyl ester hydrochloride; Formula I) as an active ingredient are known to possess utility in the treatment of heart arrhythmia. For example, U.S. Pat. Nos. 3,740,395 and 3,864,487, in the names of Gritsenko, et al., indicate that moricizine hydrochloride is superior to other antiarrhythmic drugs such as quinidine and novocainamide in that it exhibits a broader spectrum of therapeutic action and is devoid of toxic side effects.
Ethmozine.RTM. brand of moricizine hydrochloride is marketed by The Dupont Merck Pharmaceutical Company, Wilmington, DE for the treatment of heart arrhythmia.
The structure of moricizine hydrochloride is shown below: ##STR1##
Typically, moricizine hydrochloride has been synthesized by processes in which moricizine free base (10-(3-morpholinopropionyl)-phenothiazine-2-carbamic acid ethyl ester) is contacted with hydrogen chloride gas in anhydrous organic solvents such as toluene or diethyl ether. Such processes, however, are inherently hazardous due to their employment of gaseous hydrogen chloride and, further, are difficult to control.
Accordingly, there exists a need in the art for synthetic routes to moricizine hydrochloride that do not employ gaseous hydrogen chloride.